The cortisol release to 75 mg IM DMI, a noradrenergic agonist, was found to cause a significantly greater cortisol release in normal controls (n=20) in comparison to endogenous depressives (n=13); approximately 55% of the depressed group failed to release cortisol in contrast to only 5% of the normal controls. This data suggests that norepinephrine is stimulatory to cortisol in man and that a large subgroup of endogenous depressives have a noradrenergic deficit. The proposed project is aimed at 1) clarifying whether this inadequate cortisol response to DMI in a subgroup of endogenous depressives is related to their noradrenergic status (24 hr. uninary MHPG and plasma melatonin will be evaluated); 2) whether the cortisol response to DMI within endogenous depressives is related to specific clinical correlates (RDC, SADS, ect.); 3) whether non-endogenous depressives and other pathological controls also have subgroups with inadequate cortisol response to DMI; 4) whether the DMI-cortisol test is a state or trait marker. This will be evaluated by retesting depressives after recovery; 5) whether the DMI-cortisol test is related to other measures of cortisol secretion: DST (1 mg) and plasma cortisol hypersecretion. This project will allow for a detailed assessment of the DMI-cortisol test. Issues such as sensitivity and specificity will be assessed as well as associated clinical correlates. Furthermore, the relationship of multiple measures of cortisol secretion to each other, as well as the combined usefulness of these tests will be studied. Most neuroendocrine tests (DST, cortisol hypersecretion, TRH-TSH, etc.) are influenced by multiple neurotransmitters, which may have contributed to the lack of clinical correlates identified by these tests within depressives. The DMI-cortisol test may be a more specific test identifying a particular subgroup of depressives -- those with a noradrenergic deficit. It is anticipated that due to the specificity of the DMI-cortisol test, particular clinical correlates will be identified, including the responsivity of a patient to future DMI treatment.